Title

Emergence of EGFR G724S mutation in EGFR-mutant lung adenocarcinoma post progression on osimertinib.

Document Type

Article

Publication Date

9-1-2017

Keywords

Adenocarcinoma; Aged; Alleles; Amino Acid Substitution; Antineoplastic Agents; Disease Progression; Drug Resistance, Neoplasm; Exons; Fatal Outcome; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Piperazines; Protein Kinase Inhibitors; Receptor, Epidermal Growth Factor; Tomography, X-Ray Computed; Treatment Outcome; Acquired resistance; EGFR; G724S; Lung cancer; Osimertinib; T790M

Abstract

Mutations in the epidermal growth factor receptor (EGFR) are drivers for a subset of lung cancers. Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) recently approved for the treatment of T790M-positive non-small cell lung cancer (NSCLC); however, acquired resistance to osimertinib is evident and resistance mechanisms remain incompletely defined. The EGFR G724S mutation was detected using hybrid-capture based comprehensive genomic profiling (CGP) and a hybrid-capture based circulating tumor DNA (ctDNA) assays in two cases of EGFR-driven lung adenocarcinoma in patients who had progressed on osimertinib treatment. This study demonstrates the importance of both tissue and blood based hybrid-capture based genomic profiling at disease progression to identifying novel resistance mechanisms in the clinic.

Clinical Institute

Cancer

Department

Oncology

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